AZ 960 (AZ-960) is a novel, potent, selective and ATP competitive JAK2 (janus kinase) inhibitor with potential antitumor activity. It inhibits JAK2 with an IC50 and Ki of<3 nM and 0.45 nM, and displays 3-fold selectivity for JAK2 over JAK3. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. In recent studies, AZ960 demonstrates potential anti-cancer activity against adult T-cell leukemia (ATL), an aggressive malignancy of CD4+ T lymphocytes, by effectively inducing growth arrest and apoptosis in human T-cell lumphotropic virus type 1 (HTLV-1) infected T cells.

Physicochemical Properties

Molecular Formula	C18H16F2N6
Molecular Weight	354.36
Exact Mass	354.14
Elemental Analysis	C, 61.01; H, 4.55; F, 10.72; N, 23.72
CAS #	905586-69-8
Related CAS #	905586-69-8
PubChem CID	25099184
Appearance	Solid powder
Density	1.4±0.1 g/cm3
Boiling Point	515.2±50.0 °C at 760 mmHg
Flash Point	265.4±30.1 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.628
LogP	6.09
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	503
Defined Atom Stereocenter Count	1
SMILES	N(C1N=C(NC2=NNC(C)=C2)C(F)=CC=1C#N)[C@H](C1C=CC(F)=CC=1)C
InChi Key	SUNXHXDJOIXABJ-NSHDSACASA-N
InChi Code	InChI=1S/C18H16F2N6/c1-10-7-16(26-25-10)23-18-15(20)8-13(9-21)17(24-18)22-11(2)12-3-5-14(19)6-4-12/h3-8,11H,1-2H3,(H3,22,23,24,25,26)/t11-/m0/s1
Chemical Name	5-fluoro-2-[[(1S)-1-(4-fluorophenyl)ethyl]amino]-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyridine-3-carbonitrile
Synonyms	Synonym:A Z960; AZ-960; AZ960.
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Jak2 kinase is inhibited by AZ960 at a Ki of 0.45 nM. Z960 has significantly less activity against TYK2, Jak1, and 3. AZ960 has an IC50 of about 0.1 μM and is active against various kinases, including as FAK, TrkA, and Aurora-A. In human T-cell lymphotropic virus type 1, HTLV-1-infected T cells (MT-1 and MT-2), AZ960 efficiently induces growth arrest and death while downregulating the phosphorylated versions of Jak2 and Bcl-2 family proteins, including Bcl-2 and Mcl-1[2]. In recently isolated acute myeloid leukemia cells, AZ960 efficiently suppresses clonal proliferation and triggers apoptosis, which is linked to caspase 3 cleavage and downregulation of the anti-apoptotic Bcl-xL protein [1]. The AZ960 Ki for T. The value of TbERK8, or Brucei extracellular signal-regulated kinase 8, is 1.25 μM. With an IC50 of 120 nM, it inhibits TbERK8[3].
ln Vivo
Animal Protocol
References	[1]. Ikezoe T, et al. Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia. Int J Cancer. 2011 Nov 15;129(10):2512-21. [2]. Gozgit JM, et al. Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2. J Biol Chem. 2008 Nov 21;283(47):32334-43. [3]. Yang J, et al. AZ960, a novel Jak2 inhibitor, induces growth arrest and apoptosis in adult T-cell leukemia cells. Mol Cancer Ther. 2010 Dec;9(12):3386-95. [4]. Valenciano AL, et al. Discovery and antiparasitic activity of AZ960 as a Trypanosoma brucei ERK8 inhibitor. Bioorg Med Chem. 2016 Oct 1;24(19):4647-51

Solubility Data

Solubility (In Vitro)

DMSO: 71 mg/mL (200.4 mM) Water:<1 mg/mL Ethanol: 3 mg/mL (8.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8220 mL	14.1099 mL	28.2199 mL
	5 mM	0.5644 mL	2.8220 mL	5.6440 mL
	10 mM	0.2822 mL	1.4110 mL	2.8220 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.